Renal anatomy

The tables below show the anatomical relations of the kidneys:

Right kidney
Direct contact

Layer of peritoneum in-between

Right suprarenal gland

Duodenum
Colon

Liver
Distal part of small intestine

Left kidney
Direct contact

Layer of peritoneum in-between

Left suprarenal gland

Pancreas
Colon

Stomach
Spleen
Distal part of small intestine

Renal physiology
Renal blood flow is 20-25% of cardiac output
Renal cortical blood flow > medullary blood flow so, tubular cells more prone to ischaemia

Acute kidney injury

Acute tubular necrosis vs. prerenal uraemia
Prerenal uraemia - kidneys hold on to sodium to preserve volume
Pre-renal uraemia

Acute tubular necrosis

Urine sodium

< 20 mmol/L

> 30 mmol/L

Fractional sodium excretion*

< 1%

> 1%

Fractional urea excretion**

< 35%

>35%

Urine:plasma osmolality

> 1.5

< 1.1

Urine:plasma urea

> 10:1

< 8:1

Specific gravity

> 1020

< 1010

Urine

'bland' sediment

brown granular casts

Response to fluid challenge

Yes

No

*fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasma

creatinine) x 100
**fractional urea excretion = (urine urea /blood urea) / (urine creatinine/plasma creatinine) x 100
In acute tubular necrosis (ATN), urine to plasma osmolality should be less than 1.1,
urinary sodium excretion is typically more than 60 mmol/L and urinary urea excretion
less than 160 mmol/L.
If this patient had a physiological oliguria, there would still be preservation of urine
concentration, with low urinary sodium.
Both ATN and pre-renal failure can present with a fall in urine output. There is such a
marked variation in urine urea concentration, that it is seldom used as a clinical
guide.

Papillary necrosis
Causes
chronic analgesia use
sickle cell disease
2

 TB
acute pyelonephritis
diabetes mellitus
Features
fever, loin pain, haematuria
IVU - papillary necrosis with renal scarring - 'cup & spill'

Nephrotoxicity due to contrast media

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within
3 days of the intravascular administration of contrast media.
Risk factors include
known renal impairment (especially diabetic nephropathy)
age > 70 years
dehydration
cardiac failure
the use of nephrotoxic drugs such as NSAIDs
Prevention
the evidence base currently supports the use of intravenous 0.9% NaCl at a rate of 1
mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the
use of isotonic sodium bicarbonate
N-acetylcysteine (usually given orally) has been shown to reduce the incidence of
contrast-nephropathy in some studies but the evidence base is not as strong as for fluid
therapy

SLE renal complications

WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis
Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal
biopsy characteristically shows the following findings:
glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence

Diffuse proliferative SLE. Proliferation of endothelial and mesangial cells. The thickening of the capillary wall
results in a 'wire-loop' appearance. Some crescents are present.

Management
treat hypertension
corticosteroids if clinical evidence of disease
immunosuppressants e.g. azathiopine/cyclophosphamide

Lupus nephritis
Histologically, a number of different types of renal disease are recognised in SLE, with
immune-complex mediated glomerular disease being the most common.
The up to date International Society of Nephrology/Renal Pathology Society 2003
classification divides these into six different patterns:
I - minimal mesangial
II - mesangial proliferative
III - focal
IV - diffuse
V - membranous
VI - advanced sclerosis

I - minimal mesangial:
Light microscopy

Glomeruli appear normal, but

Immunofluorescence demonstrates mesangial immune deposits.

II - Mesangial proliferative nephritis
Presents clinically as microscopic haematuria and/or proteinuria.
Hypertension is incommon and nephrotic syndrome and renal impairment are very rarely
seen.
Biopsy demonstrates:
Segmental areas of increased mesangial matrix and cellularity, with mesangial immune
deposits.
A few isolated subepithelial or subendothelial deposits may be visible by
immunofluorescence.
The prognosis is good and specific treatment is only indicated if the disease progresses.
III - Focal disease:
More advanced, but still affects < 50% of glomeruli.
Haematuria and proteinuria is almost always seen
nephrotic syndrome, hypertension and elevated creatinine may be present.
Biopsy demonstrates:
Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis
involving < 50% of glomeruli,
typically with focal subendothelial immune deposits,
with or without mesangial alterations
It is further subdivided:
A: Active lesions: focal proliferative lupus nephritis
A/C: Active and chronic lesions: focal proliferative and sclerosing lupus nephritis
C: Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis
Prognosis is variable.

IV - Diffuse glomerulonephritis:
The most common and severe form of lupus nephritis.
Haematuria and proteinuria are almost always present, and
6

 nephrotic syndrome, hypertension and renal impairment common.

Biopsies demonstrate
Active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis
involving > 50% of all glomeruli,
typically with diffuse subendothelial immune deposits,
with or without mesangial alterations
This class is divided into:
Diffuse segmental (IV-S) when more than 50% of the involved glomeruli have
segmental lesions, and
Diffuse global (IV-G) when more than 50% of involved glomeruli have global lesions.
(Segmental is defined as a glomerular lesions that involves less than half of the glomerular
tuft)
IV-S (A): Active lesions, diffuse segmental proliferative lupus nephritis
IV-G (A): Active lesions, diffuse global proliferative
IV-S (A/C): Active and chronic lesions, diffuse segmental proliferative and sclerosing lupus
nephritis
IV-S (C): Chronic inactive lesions with scars, diffuse segmental sclerosing lupus nephritis
IV-G (C): Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis
Immunosuppressive therapy is required in these cases to prevent progressive to end-stage
renal failure.
V - Membranous lupus nephritis:
Patients with membranous lupus nephritis tend to present with nephrotic syndrome.
Microscopic haematuria and hypertension may also be seen.
Biopsies show
Global or segmental subepithelial immune deposits or their morphologic sequelae,
with or without mesangial alterations
It may occur in combination with class III or IV, in which case both are diagnosed.
Progression is variable, and immunosuppression is not always needed.
VI - advanced sclerosis: >90% of glomeruli are globally sclerosed without residual activity.
With regard to the management of lupus nephritis a biopsy is indicated in those patients with
abnormal urinalysis and/or reduced renal function.
7

 This can provide a histological classification as well as information regarding activity,

chronicity and prognosis.
Cyclophosphamide, mycophenolate mofetil and azathioprine reduce mortality in
proliferative forms of lupus glomerulonephritis.

Rhabdomyolysis
Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged
epileptic seizure and is found to have acute renal failure on admission
Features
acute renal failure with disproportionately raised creatinine
elevated CK
myoglobinuria
hypocalcaemia (myoglobin binds calcium)
elevated phosphate (released from myocytes)
Causes
seizure
collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
ecstasy (MDMA)
crush injury
McArdle's syndrome
drugs: statins
Management
IV fluids to maintain good urine output
urinary alkalinization is sometimes used

Acute vs. chronic renal failure

Best way to differentiate is renal ultrasound, most patients with CRF have bilateral small
kidneys
Exceptions
autosomal dominant polycystic kidney disease ADPCK
diabetic nephropathy
amyloidosis
HIV-associated nephropathy
Other features suggesting CRF rather than ARF
hypocalcaemia (due to lack of vitamin D)

Chronic kidney disease causes

Common causes of chronic kidney disease
diabetic nephropathy
chronic glomerulonephritis
chronic pyelonephritis
hypertension
adult polycystic kidney disease

Chronic kidney disease: eGFR and classification

Serum creatinine may not provide an accurate estimate of renal function due to differences in
muscle. For this reason formulas were develop to help estimate the glomerular filtration rate
(estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal
Disease (MDRD) equation, which uses the following variables:
serum creatinine
age
gender
ethnicity
Factors which may affect the result
pregnancy
muscle mass (e.g. amputees, body-builders)
eating red meat 12 hours prior to the sample being taken
CKD may be classified according to GFR:
CKD stage

GFR range

> 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests*
are normal, there is no CKD)

60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no
CKD)

3a

45-59 ml/min, a moderate reduction in kidney function

3b

30-44 ml/min, a moderate reduction in kidney function

15-29 ml/min, a severe reduction in kidney function

< 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed

*i.e. normal U&Es and no proteinuria

Anaemia in Chronic kidney disease

10

 Patients with chronic kidney disease (CKD) may develop anaemia due to a variety of factors,
the most significant of which is reduced erythropoietin levels. This is usually a normochromic
normocytic anaemia and becomes apparent when the GFR is less than 35 ml/min (other
causes of anaemia should be considered if the GFR is > 60 ml/min).
Anaemia in CKD predisposes to the development of LVH - associated with a threefold
increase in mortality in renal patients
Causes of anaemia in renal failure:
reduced erythropoietin levels - the most significant factor
reduced erythropoiesis due to toxic effects of uraemia on bone marrow
reduced absorption of iron
anorexia/nausea due to uraemia
reduced red cell survival (especially in haemodialysis)
blood loss due to capillary fragility and poor platelet function
stress ulceration leading to chronic blood loss
Management:
the 2011 NICE guidelines suggest a target haemoglobin of 10 - 12 g/dl
determination and optimisation of iron status should be carried out prior to the
administration of erythropoiesis-stimulating agents (ESA)
Many patients, especially those on haemodialysis, will require IV iron
ESAs such as erythropoietin and darbepoetin should be used in those 'who are likely to
benefit in terms of quality of life and physical function'

Erythropoietin
Erythropoietin is a haematopoietic growth factor that stimulates the production of erythrocytes.
The main uses of erythropoietin are to treat the anaemia associated with CKD and that
associated with cytotoxic therapy.
Side-effects of erythropoietin
accelerated hypertension potentially leading to encephalopathy and seizures (blood
pressure increases in 25% of patients)
bone aches
flu-like symptoms
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 skin rashes, urticaria (pruritus of Hyperviscosity Syndrome )

pure red cell aplasia (due to antibodies against erythropoietin)
The risk is greatly reduced with darbepoetin (Aranesp)
raised PCV increases risk of thrombosis (e.g. Fistula)
iron deficiency 2nd to increased erythropoiesis

There are a number of reasons why patients may fail to respond to erythropoietin therapy:
iron deficiency
inadequate dose
concurrent infection/inflammation (MIA)
hyperparathyroid bone disease
aluminium toxicity

Due to the mild chronic inflammatory nature of chronic renal disease a ferritin <100 g/L
should be considered an indicator of absolute iron deficiency.
Transferrin saturation <20% should be considered a marker of functional iron deficiency
when the ferritin is >100 g/L.
Transferrin saturation - Circulating transferrin normally is about one-third saturated with iron
(i.e., Fe/TIBC = 1/3, when both are expressed as micrograms of iron per 100 mL of plasma).
Conditions in which transferrin saturation is reduced (expressed as a percentage)
include those in which the supply of iron to the plasma from the macrophage and other
storage sites is reduced. These include:
Iron deficiency anemia
The anemia of chronic disease (anemia of chronic inflammation), and
Some patients with a ferroportin mutation
transferrin saturation is increased (expressed as a percentage) in those conditions in
which the supply of iron is excessive or is greater than the current demand. These include:
Most cases of hereditary and acquired hemochromatosis
12

Aplastic anemia,
bone marrow suppression
Sideroblastic anemias
Ineffective erythropoiesis
Liver disease with reduced transferrin synthesis, and
Monoclonal immunoglobulin with antitransferrin activity (rare).

It is recommended that patients with anaemia secondary to chronic renal failure should
have:
a ferritin level maintained at 200-500 g/L and either
transferrin saturations >20% or
percentage hypochromic red cells <6%
Where patients have absolute iron deficiency oral iron supplementation may be adequate.
However where there is functional iron deficiency, intravenous iron replacement is
recommended.
Blood transfusion may be indicated where there are severe symptoms of anaemia or a
particularly low haemoglobin level.
Where possible blood transfusion should be avoided in patients who may be candidates
for transplantation as the development of antibodies to alloantigens may make future
transplantation more problematic.
Erythropoietin should be commenced when anaemia has reached a level requiring
treatment and usually only after the patient has had their iron stores adequately replaced.

13

Chronic kidney disease: hypertension

The majority of patients with chronic kidney disease (CKD) will require more than two drugs
to treat hypertension.
ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g.
diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in
glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that
a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable,
although any rise should prompt careful monitoring and exclusion of other causes (e.g.
NSAIDs). A rise greater than this may indicate underlying renovascular disease
Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR
falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High
doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis)
then consideration should be given to temporarily stopping the drug
*the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min

14

Proteinuria
Proteinuria is an important marker of chronic kidney disease, especially for diabetic
nephropathy.
NICE recommend using albumin: creatinine ratio in preference to protein: creatinine
ratio (PCR) when identifying patients with proteinuria as it has greater sensitivity.
For quantification and monitoring of proteinuria, PCR can be used as an alternative, although
ACR is recommended in diabetics.
Urine reagent strips are not recommended unless they express the result as an ACR
Approximate equivalent values
ACR (mg/mmol)

PCR (mg/mmol)

Urinary protein excretion (g/24 h)

30

50

0.5

70

100

Collecting an ACR sample

by collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in
order to detect or quantify proteinuria
should be a first-pass morning urine specimen
if the initial ACR is > 30 mg/mmol and < 70 mg/mmol, confirm by a subsequent early
morning sample. If the initial ACR is > 70 mg/mmol a repeat sample need not be tested

15

Interpreting the ACR results

in non-diabetics an ACR > 30 mg/mmol is considered clinically significant proteinuria
in diabetics microalbuminuria (ACR > 2.5 mg/mmol in men and ACR > 3.5 mg/mmol in
women) is considered clinically significant

BP targets
CKD with proteinuria ACR 70 mg/mmol or diabetes ---- blood pressure target < 130/80 mmHg.
The NICE guidelines recommend that a blood pressure target < 140/90 mmHg should be used in
non-diabetic patients with CKD and an ACR <70 mg/mmol.
NOT for lower systolic (<120 mmHg) or diastolic (<60 mmHg)

Hyperkalaemia
Plasma potassium levels are regulated by a number of factors including aldosterone, acidbase balance and insulin levels.
Metabolic acidosis is associated with hyperkalaemia as H+ and K+ ions compete with each
other for exchange with Na+ ions across cell membranes and in the distal tubule.
Untreated hyperkalaemia may cause life-threatening arrhythmias.
Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs
stopped (e.g. ACE inhibitors).
ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened
QRS leading to a sinusoidal pattern and asystole.
Causes of hyperkalaemia:
acute renal failure
drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers,
spironolactone, cyclosporine, heparin**
metabolic acidosis
16

 Addison's
rhabdomyolysis
massive blood transfusion
Foods that are high in potassium:
salt substitutes (i.e. Contain potassium rather than sodium)
bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
*beta-blockers interfere with potassium transport into cells and can potentially cause
hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are
sometimes used as emergency treatment
**both unfractionated and LMWH can cause hyperkalaemia. This is thought to be caused by
inhibition of aldosterone secretion
Management: may be categorized by the aims of treatment
Stabilization of the cardiac membrane
intravenous calcium gluconate
Short-term shift in potassium from ECF to ICF compartment
combined insulin/dextrose infusion
nebulised salbutamol
Removal of potassium from the body
calcium resonium (orally or enema)
loop diuretics
dialysis

The initiation of emergency renal replacement therapy is usually required for:

1)
2)
3)
4)

Acute life threatening hyperkalaemia which is resistant to treatment

Development of metabolic acidosis which is non-responsive to fluid.
Development of fluid overload, which may manifest itself as pulmonary oedema.
Development of uraemia which may manifest itself as pericarditis, neuropathy and
confusional state.
17

Primary hyperparathyroidism is associated with hypercalcaemia and an inappropriately

raised parathyroid hormone, the phosphate level is typically low.
Secondary hyperparathyroidism is associated with hypocalcaemia and an appropriately
elevated parathyroid hormone level, the phosphate level is variable depending upon the
aetiology (high in renal failure, low in vitamin D deficiency).
Hypercalaemia of malignancy and iatrogenic hypercalcaemia would both be associated
with a high calcium and low parathyroid hormone level.

18

Acid Base Balance

The anion gap is a simple method for discerning causes of metabolic acidosis.
It relies on the fact that the concentration of cations in plasma must equal the
concentration of anions.
Cations have positive charge, anions have negative charge.
[Cations] = [Anions]
Most ions are unmeasured and individually have a low concentration.
The measured ions in sufficient concentration are sodium, potassium, chloride and
bicarbonate. Therefore:
[Na] + [K] + [unmeasured cations] = [Cl] + [HCO3] [unmeasured anions]
And rearranging:
([Na] + [K]) - ([Cl] + [HCO3]) = [unmeasured anions] - [unmeasured cations].

The anion gap is the difference between unmeasured anions and unmeasured cations
In health is between 10-18 mmol/l.
This value is helpful in discerning causes of metabolic acidosis,
As if it is raised the acidosis is due to an unmeasured ion - such as lactate, ketones,
salicylate in lactic acidosis, diabetic ketoacidosis and aspirin overdose respectively, and
methanol or ethylene glycol poisoning
A normal anion gap suggests an acidosis due to bicarbonate or chloride handling such as renal tubular acidosis, diarrhoea, pancreatic fistula, ammonium chloride
ingestion or acetazolamide.

19

 A metabolic alkalosis may be seen in vomiting, from other diuretics or excessive

bicarbonate or antacid therapy.
Respiratory acidosis is defined by a raised pCO2 and is typically related to type 2
respiratory failure. It is seen in severe COPD, asthma, pneumonia or pulmonary oedema
and hypoventilation due to sedatives, muscular disease (for example, myasthenia gravis)
or chest wall trauma.
Respiratory alkalosis is seen in any cause of hyperventilation, either due to anxiety, or in
hypoxic states such as asthma where adequate ventilation is preserved.
Carbonic anhydrase catalyses the first part of the reversible reaction in which carbon
dioxide and water are converted to carbonic acid (and vice versa):
CO2 + H2O H+ + HCO3 In the kidney, carbonic anhydrase is found in the proximal convoluted tubule.
The equation is normally shifted to the left allowing the formed carbon dioxide to diffuse
back into the systemic circulation.
In the presence of a carbonic anhydrase inhibitor, such as acetazolamide, the equation is
shifted to the right and more H+ and HCO3- is produced.
The H+ is reabsorbed alongside chloride ions. However, the bicarbonate is passed in the
urine as it is not easily absorbed in the nephron.
This results in a hyperchloraemic, normal anion gap metabolic acidosis.
This effect can be used therapeutically to prevent acute mountain sickness. Whereas
normally the hypoxic high altitude would stimulate ventilation resulting in a respiratory
alkalosis, acetazolamide use causes net renal excretion of bicarbonate, correcting this
abnormality.

20

 With respiratory alkalosis the kidneys would physiologically excrete bicarbonate, but this
takes two to three days. Acetazolamide speeds this process.

Causes of respiratory alkalosis:

Central causes - stroke, meningitis, CNS tumour
Drugs - salicylates
Anxiety
Pregnancy.
Causes of metabolic alkalosis:
Vomiting - anorexia nervosa, gastric outlet obstruction
Ingestion of base
Prolonged hypokalaemia of any cause - the kidney allows H+ to be lost in an effort
to retain K+. Diuretic therapy is a common example.
Burns.

Renal tubular acidosis

All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic metabolic
acidosis (normal anion gap)
Type 1 RTA (distal)
inability to generate acid urine (secrete H+) in distal tubule
causes hypokalaemia
complications include nephrocalcinosis and renal stones
causes include idiopathic, RA, SLE, Sjogren's

21

Abdominal x-ray showing nephrocalcinosis - a classical finding in type 1 RTA

Type 2 RTA (proximal)

decreased HCO3- reabsorption in proximal tubule
causes hypokalaemia
complications include osteomalacia
causes include:
1)
2)
3)
4)
5)

idiopathic,
as part of Fanconi syndrome,
Wilson's disease,
cystinosis,
outdated tetracyclines

Type 4 RTA (hyperkalaemic) hyporeninenimic hypoaldosteronimic

reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium
excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes

Fanconi syndrome
Fanconi syndrome describes a generalised disorder of renal tubular transport resulting in:
type 2 (proximal) renal tubular acidosis
aminoaciduria
glycosuria
22

 phosphaturia
osteomalacia
Causes
cystinosis (most common cause in children)
Sjogren's syndrome
Wilson's disease
multiple myeloma
nephrotic syndrome

Diabetic nephropathy
23

 commonest cause of end-stage renal disease (ESRD) in the western world

33% of patients with type 1 diabetes mellitus have diabetic nephropathy by the age of 40
years
approximately 5-10% of patients with type 1 diabetes mellitus develop (ESRD)
The pathophysiology is poorly understood, however:
changes to the haemodynamics of the glomerulus is thought to be key, which leads to an
increased glomerular capillary pressure
Histological changes include:

BM thickening,
capillary obliteration,
mesangial widening.
Nodulular hyaline areas develop in the glomuli - Kimmelstiel-Wilson nodules

Thickening of the basement membrane is seen alongside multiple Kimmelstiel-Wilson nodules

Severe arteriolosclerosis is seen in the afferent arteriole on the left of the slide.
Multiple, smaller acellular nodules are seen in the glomerulus - Kimmelstiel-Wilson nodules.
The tubular basement membrane is also thickened
24

Risk factors for developing diabetic nephropathy

Modifiable

Non-modifiable

Hypertension
Hyperlipidaemia
Smoking
Poor glycaemic control
Raised dietary protein

Male sex
Duration of diabetes
Genetic predisposition (e.g. ACE gene
polymorphisms)

Stages of Diabetic nephropathy:

Diabetic nephropathy may be classified as occurring in five stages*:
Stage 1
hyperfiltration: increase in GFR
may be reversible
Stage 2 (silent or latent phase)
most patients do not develop microalbuminuria for 10 years
GFR remains elevated
Stage 3 (incipient nephropathy)
microalbuminuria (albumin excretion of 30-300 mg/day, dipstick negative)(ACR >2.5)
Stage 4 (overt nephropathy)
persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive)
hypertension is present in most patients
histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (KimmelstielWilson nodules)
Stage 5
ESRD, GFR typically < 10ml/min
RRT needed
25

The timeline given here is for type 1 diabetics. Patients with type 2 diabetes mellitus (T2DM)
progress through similar stages but in a different timescale - some T2DM patients may progress
quickly to the later stages

ARPKD
Autosomal recessive polycystic kidney disease (ARPKD) is much less common than
autosomal dominant disease (ADPKD).
It is due to a defect in a gene located on chromosome 6
Diagnosis may be made on prenatal ultrasound or in early infancy with abdominal masses
and renal failure.
Newborns may also have features consistent with Potter's syndrome secondary to
oligohydramnios.
ESRD develops in childhood.
Patients also typically have liver involvement, for example portal and interlobular fibrosis.
Renal biopsy typically shows multiple cylindrical lesions at right angles to cortical surface.

Autosomal dominant polycystic kidney disease (ADPKD)

The most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians.
Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and
polycystin-2 respectively

ADPKD type 1

ADPKD type 2

85% of cases

15% of cases

Chromosome 16

Chromosome 4

Presents with renal failure earlier

26

 The screening investigation for relatives is abdominal ultrasound (start at 18 years)

Formal screening for AKPD occurs in early adulthood, usually with a renal ultrasound scan.
Its sensitivity approaches 100% in those over 30 years, but falls to less than 70% under this
age.
Ultrasound diagnostic criteria (in patients with positive family history)
two cysts, unilateral or bilateral, if aged < 30 years
two cysts in both kidneys if aged 30-59 years
four cysts in both kidneys if aged > 60 years
Features
hypertension
recurrent UTIs
abdominal pain
renal stones
haematuria
chronic kidney disease
Extra-renal manifestations
Liver cysts (70%)
Berry aneurysms (8%)
cardiovascular system:
mitral valve prolapse,
mitral/tricuspid incompetence,
aortic root dilation, aortic dissection
cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary

On average, patients progress to end stage renal failure between the ages
of 40 and 60 years.
In these patients the renal function usually deteriorates in a gradual
fashion, usually with a drop in creatinine clearance of 5/6 ml/min/year (at
least 10 years for this patient or possibly sooner if BP not adequately
managed).
Treatment should include a high fluid intake (to prevent the formation of
renal stones or blood clots) and regular follow up of blood pressure and
renal function. Loin pain should be treated symptomatically, and
27

hypertension should be managed with standard antihypertensive

medications.
Haematuria should be treated conservatively.
Urinary tract infections should be treated with lipophillic drugs (for example,
ciprofloxacin, trimethoprim-sulphamethoxazole) as they have the best
penetration into cyst fluid.
It is an autosomal dominant disease, therefore the offspring of an affected
patient has a 50% chance of inheriting the disease. The patient should be
offered genetic counselling, despite the fact that the disease has a variable
clinical course even between affected family members.

Extensive cysts are seen in an enlarged kidney

28

CT showing multiple cysts of varying sizes in the liver, and bilateral kidneys with little remaining normal renal
parenchyma.

29

Haematuria
The management of patients with haematuria is often difficult due to the absence of widely
followed guidelines.
It is sometimes unclear whether patients are best managed in primary care, by urologists or

by nephrologists.
The terminology surrounding haematuria is changing.
Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria
whilst macroscopic haematuria is termed visible haematuria
Non-visible haematuria is found in around 2.5% of the population.

Causes of transient or spurious non-visible haematuria

UTI
menstruation
sexual intercourse
vigorous exercise (this normally settles after around 3 days)
Spurious causes - red/orange urine, where blood is not present on dipstick
foods: beetroot, rhubarb
drugs: rifampicin, doxorubicin, Metronidazole
Causes of persistent non-visible haematuria
1) cancer (bladder, renal, prostate)
2) stones
3) benign prostatic hyperplasia
4) prostatitis
5) urethritis e.g. Chlamydia
6) renal causes: IgA nephropathy, thin basement membrane disease
Management:
Current evidence does not support screening for haematuria.
The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the
general population hence these patients should also be investigated.

30

Testing
1) urine dipstick is the test of choice for detecting haematuria
persistent non-visible haematuria is often defined as blood being present in 2 out of 3
samples tested 2-3 weeks apart
2) BP , RFTs, and albumin:creatinine (ACR) or protein:creatinine ratio (PCR) should also be
checked
3) urine microscopy may be used but time to analysis significantly affects the number of RBCs
detected

NICE urgent cancer referral guidelines

1) of any age with painless macroscopic haematuria
2) patients under the age of 40 years with normal renal function, no proteinuria and who are
normotensive do not need to be referred and may be managed in primary care
3) aged 40 years and older who present with recurrent or persistent UTI associated with
haematuria
4) aged 50 years and older who are found to have unexplained microscopic haematuria

31

Alport's syndrome
Usually inherited in an X-linked dominant pattern*.
It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal
glomerular-basement membrane (GBM).
The disease is more severe in males
females rarely developing renal failure
Patients with Alport syndrome are at risk of developing antiglomerular basement

membrane disease (Goodpasture's disease) following transplantation, as their immune

systems have never been exposed to type IV collagen and hence lack tolerance.
Favourite question is an Alport's patient with a failing renal transplant. This may be
caused by presence of anti-GBM antibodies leading to Goodpasture's syndrome like
picture
Alport's syndrome usually presents in childhood.
Type IV collagen is found in the basement membrane of the kidney, inner ear and eye, so

therefore extra-renal manifestations include bilateral sensorineural deafness and ocular

abnormalities such as corneal dystrophies and lens abnormalities.
The following features may be seen:
microscopic and macroscopic haematuria with or without proteinuria
progressive renal failure
bilateral sensorineural deafness
lenticonus: protrusion of the lens surface into the anterior chamber
retinitis pigmentosa
renal biopsy: splitting of lamina densa seen on EM
32

 The disease is X-linked dominant in 85% of cases

10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal
dominant variants existing
the most common genetic abnormality is a mutation in the COL4A5 gene (involved in type

IV collagen synthesis) on the X chromosome

COL4A3 and COL4A4 (genes also involved in type IV collagen synthesis) are located on
chromosome 2, explaining why this disease may also have autosomal recessive or
dominant inheritance.
As Alport syndrome is X linked in 85% of cases. Therefore, as only the Y
chromosome is passed from father to son there is no chance of the son having the
disease from only affected father

Glomerulonephritides
Knowing a few key facts is the best way to approach the difficult subject of glomerulonephritis:
Minimal change disease
Typically a child with nephrotic syndrome (accounts for 80%)
causes: Hodgkin's, NSAIDs
good response to steroids
Membranous glomerulonephritis
presentation: proteinuria / nephrotic syndrome / chronic kidney disease
cause: infections, rheumatoid drugs, malignancy
1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease
Focal segmental glomerulosclerosis
may be idiopathic or secondary to HIV, heroin
presentation: proteinuria / nephrotic syndrome / chronic kidney disease
33

IgA nephropathy - aka Berger's disease, mesangioproliferative GN

typically young adult with haematuria following an URTI
Diffuse proliferative glomerulonephritis
classical post-streptococcal glomerulonephritis in child
presents as nephritic syndrome / acute kidney injury
most common form of renal disease in SLE
Rapidly progressive glomerulonephritis - aka crescentic glomerulonephritis
rapid onset, often presenting as acute kidney injury
causes include Goodpasture's, ANCA positive vasculitis
Mesangiocapillary glomerulonephritis (membranoproliferative)
type 1: cryoglobulinaemia, hepatitis C
type 2: partial lipodystrophy

Glomerulonephritis and low complement

1) post-streptococcal glomerulonephritis
2) subacute bacterial endocarditis
3) systemic lupus erythematosus
4) mesangiocapillary glomerulonephritis

Nephrotic syndrome
Triad of:
1) Proteinuria (> 3g/24hr) causing
2) Hypoalbuminaemia (< 30g/L) and
3) Oedema
Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels
predispose to thrombosis.
34

 Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

Nephrotic syndrome complications:

increased risk of infection due to urinary immunoglobulin loss
increased risk of thromboembolism related to loss of antithrombin III and plasminogen in
the urine
hyperlipidaemia
hypocalcaemia (vitamin D and binding protein lost in urine)
acute renal failure

35

Minimal change disease

Always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in
adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
1) drugs: NSAIDs, rifampicin
2) Hodgkin's lymphoma, thymoma
3) infectious mononucleosis
Pathophysiology
T-cell and cytokine mediated damage to the GBM polyanion loss
the resultant reduction of electrostatic charge increased glomerular permeability to
serum albumin
Features
nephrotic syndrome
normotension - hypertension is rare
highly selective proteinuria: only intermediate-sized proteins such as albumin and
transferrin leak through the glomerulus
renal biopsy: electron microscopy shows fusion of podocytes
Management
majority of cases (80%) are steroid responsive
cyclophosphamide is the next step for steroid resistant cases
Prognosis is overall good, although relapse is common. Roughly:
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood

36

Membranous glomerulonephritis

The commonest type of glomerulonephritis in adults

The third most common cause of ESRF.
It usually presents with nephrotic syndrome or proteinuria.

Renal biopsy demonstrates:

EM: the basement membrane is thickened with subepithelial electron dense deposits.
This creates a 'spike and dome' appearance
Causes
1) idiopathic
2) infections: hepatitis B, malaria, syphilis
3) malignancy: lung cancer, lymphoma, leukaemia
4) drugs: gold, penicillamine, NSAIDs
5) autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis,
rheumatoid
Prognosis - rule of thirds
one-third: spontaneous remission
one-third: remain proteinuric (respond to cytotoxics)
one-third: develop ESRF
Good prognostic features include:
1) female sex,
2) young age at presentation and
37

3) asymptomatic
4) proteinuria of a modest degree at the time of presentation
Management
1) Immunosuppression:
A combination of corticosteroid + another agent such as chlorambucil is often used
corticosteroids alone have not been shown to be effective
2) blood pressure control: ACE inhibitors have been shown to reduce proteinuria
3) consider anticoagulation

Silver-stained section showing thickened basement membrane, subepithelial spikes

Focal segmental glomerulosclerosis

A cause of nephrotic syndrome and chronic kidney disease.
It generally presents in young adults.
Causes
1) idiopathic
2) secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
3) HIV
4) heroin
5) Alport's syndrome
6) sickle-cell
Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal
transplants.

38

Sclerosis of the glomerulus is seen next to Bowman's capsule

Sclerosis is seen in the perihilar region of the glomerulus

IgA nephropathy
also called Berger's disease or mesangioproliferative glomerulonephritis
commonest cause of glomerulonephritis worldwide
thought to be caused by mesangial deposition of IgA immune complexes
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
Histology:
mesangial hypercellularity,
positive immunofluorescence for IgA & C3

39

Proliferation and hypercellularity of the mesangium is seen in the glomerulus

Presentations
young male, recurrent episodes of macroscopic haematuria
typically associated with mucosal infections e.g., URTI
nephrotic range proteinuria is rare
renal failure
Associated conditions
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura
Management
steroids/immunosuppressants not be shown to be useful
Prognosis
25% of patients develop ESRF
markers of good prognosis: frank haematuria
markers of poor prognosis:
1)
2)
3)
4)
5)

male gender,
proteinuria (especially > 2 g/day),
hypertension, hyperlipidaemia
smoking, ,
ACE genotype DD

Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis

40

1) post-streptococcal glomerulonephritis is associated with low complement levels

2) main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria
can occur)
3) there is typically an interval between URTI and the onset of renal problems in poststreptococcal glomerulonephritis

Henoch-Schonlein purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis.
There is a degree of overlap with IgA nephropathy (Berger's disease).
HSP is usually seen in children following an infection.
Features
1) palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms
and legs (preceded by URTI group A streptococcal )
2) abdominal pain
3) polyarthritis
4) features of IgA nephropathy may occur e.g. haematuria, renal failure

41

Immunostaining for IgA in a patient with HSP

Treatment
analgesia for arthralgia
Treatment of nephropathy is generally supportive.
There is inconsistent evidence for the use of steroids and immunosuppressants (used if
severe or deteriorating disease)
All patients with HTN and proteinuria (> 1 g/day-) should be started on (ACE) inhibitor,
Once the BP has been controlled she should have a renal biopsy, and if this showed changes of

a crescentic glomerulonephritis (GN), then an immunosuppression regime similar to that used

in renal vasculitis should be started (high dose steroids +/- cyclophosphamide).

Prognosis
usually excellent, HSP is a self-limiting condition, especially in children without renal
involvement
around 1/3rd of patients have a relapse

42

Membranoproliferative glomerulonephritis
also known as mesangiocapillary glomerulonephritis
may present as nephrotic syndrome, haematuria or proteinuria
poor prognosis
Type 1
accounts for 90% of cases
subendothelial immune deposits of electron dense material resulting in a 'tram-track'
appearance
cause: cryoglobulinaemia, hepatitis C
Type 2 - 'dense deposit disease' DDD
causes: partial lipodystrophy, factor H deficiency
reduced serum complement
C3b nephritic factor (an antibody against C3bBb) found in 70%
43

Type 3
causes: hepatitis B and C
Management
steroids may be effective

Vasculitis
See rheumatology

Granulomatosis with polyangiitis

(Wegener's granulomatosis)
Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis.
an autoimmune condition associated with a necrotizing granulomatous vasculitis, affecting
both the upper and lower respiratory tract as well as the kidneys
Features:
1) upper respiratory tract: epistaxis, sinusitis, nasal crusting
2) lower respiratory tract: dyspnoea, haemoptysis, cavitating lesions
3) rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
4) saddle-shape nose deformity
44

5) also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions
Investigations:
1) cANCA positive in > 90%, pANCA positive in 25%
2) chest x-ray: wide variety of presentations, including cavitating lesions
3) renal biopsy: epithelial crescents in Bowman's capsule
Management:
1) steroids
2) cyclophosphamide (90% response)
3) plasma exchange
4) median survival = 8-9 years
Chest x-ray from a young male patient
with granulomatosis with polyangiitis.
Whilst the changes are subtle it
demonstrates a number of ill-defined
nodules the largest of which projects over
the dome of the right hemidiaphragm.
This nodule appears to have a central
lucency suggesting cavitation
CT of the same patient showing the
changes in a much more obvious way,
confirming the presence of at least 2
nodules, the larger of the two having a
large central cavity and air-fluid level

Haemolytic uraemic syndrome (HUS)

Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:
1) acute renal failure

2) microangiopathic haemolytic anemia

3) thrombocytopenia
Causes:

post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohaemorrhagic')

45

tumours

pregnancy

ciclosporin, the Pill

SLE, HIV

Investigations:

full blood count: anemia, thrombocytopaenia, fragmented blood film

U&E: acute renal failure

stool culture

Management:

treatment is supportive e.g. Fluids, blood transfusion and dialysis if required

there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients

The indications for plasma exchange in HUS are complicated. As a general rule plasma
exchange is reserved for severe cases of HUS not associated with diarrhea

HUS is a complication of infection with verocytotoxin producing Escherichia coli usually of

the serotype 0157:H7.
Toxins produced in the intestine enter the blood and bind to endothelial cells in target organs.
Endothelial cell damage leads to platelet and fibrin deposition with resultant fragmentation
of circulating red blood cells and microvascular occlusion.
The syndrome has also been reported after infections with coxsackie, echovirus and Shigella.

HUS is characterised by the sudden onset of haemolytic anaemia with fragmentation of

red blood cells, thrombocytopenia and acute renal failure after a prodromal illness of acute
gastroenteritis often with bloody diarrhoea.
Clinical signs include increasing pallor, haematuria, oliguria and purpura. Jaundice is
occasionally seen. Hypertension may be present.
Typical results show an anaemia, thrombocytopenia, and often a neutrophilia. Blood film
shows fragmented erythrocytes.
There is normal coagulation and fibrinogen.
Neurological complications include: Stroke, seizure and coma occur in 25% of patients
Rarely pancreatitis, and Pleural and pericardial effusions.
Approximately 5% of patients will develop end stage renal failure.
Long term renal sequelae range from proteinuria to chronic renal failure.
Therapy is supportive with:
Correction of anaemia
Correction of uraemia by early dialysis
Strict fluid balance
46

 Treatment of hypertension.
Major differential diagnosis is:
1)
Sepsis with DIC - presents with abnormalities of clotting parameters.
2)

TTP - thrombotic thrombocytopenic purpura presents with microangiopathic haemolytic

anaemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal disease.
Renal abnormalities tend to be more severe in HUS.
Although once considered variants of a single syndrome, recent evidence suggests that
the pathogenesis of TTP and HUS is different.
Patients with TTP lack a plasma protease that is responsible for the breakdown of von
Willebrand factor (vWF) multimers and these accumulate in the plasma. The activity of this
protease is normal in patients with HUS.
Until the test for vWF protease activity becomes available, differentiation between HUS
and TTP is based on the presence of central nervous system involvement in TTP and the
more severe renal involvement in HUS.
In HUS 90% of patients are children and a history of prodromal diarrhoeal illness is more
common.
The therapy of choice for TTP is plasma exchange with fresh frozen plasma.

HIV: renal involvement

Renal involvement in HIV patients may occur as a consequence of treatment or the virus
itself.
Protease inhibitors such as indinavir can precipitate intratubular crystal obstruction
HIV-associated nephropathy (HIVAN) accounts for up to 10% of ESRD cases in the US.
Antiretroviral therapy has been shown to alter the course of the disease.
There are five key features of HIVAN:
1) normal or large kidneys
2) normotension
3) massive proteinuria
4) elevated urea and creatinine
5) FSGS with focal or global capillary collapse on renal biopsy

Cholesterol embolisation
cholesterol emboli may break off causing renal disease
seen more commonly in arteriopaths, abdominal aortic aneurysms
47

Features
1) eosinophilia
2) purpura
3) livedo reticularis
4) renal failure

Plasma exchange
Indications for plasma exchange
Guillain-Barre syndrome
myasthenia gravis
TTP/HUS
cryoglobulinaemia
Goodpasture's syndrome
ANCA positive vasculitis e.g. Wegener's, Churg-Strauss
hyperviscosity syndrome e.g. secondary to myeloma, monoclonal gammopathy
In most conditions 5% albumin is the plasma substitute of choice , except for TTP where we use
FFP as it has a therapeutic role in replacing the missing factor, ADAMTS-13.

Peritoneal dialysis
Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stopgap to haemodialysis or for younger patients who do not want to have to visit hospital three times
a week.
The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves
four 2-litre exchanges/day.
Complications:
1) Peritonitis:
Coagulase-negative staphylococci such as Staphylococcus epidermidisis the most
common cause.
Staphylococcus aureus is another common cause
2) sclerosing peritonitis
48

PD peritonitis

PD peritonitis is an emergency and requires prompt broad spectrum antibiotic therapy.

Antibiotics delivered through the intra-peritoneal route are preferred to intravenous route.
Whilst antibiotic polices differ among hospitals, initial antibiotic regimes should cover Gram
positive (including MRSA) and Gram negative organisms.
Although laboratory tests are helpful, antibiotic therapy should not be delayed for the
results of these tests (CBC, CRP, C/Ss).

Renal vascular disease

Renal vascular disease is most commonly due to atherosclerosis (> 95% of patients).
It is associated with risk factors such as smoking and HTN that cause atheroma elsewhere in
the body.
It may present as HTN, CKD or 'flash' pulmonary oedema.
In younger patients however fibromuscular dysplasia (FMD) needs to be considered.
FMD is more common in young women and characteristically has a 'string of beads'
appearance on angiography.
Patients respond well to balloon angioplasty ?????
Investigation
MR angiography is now the investigation of choice
CT angiography
conventional renal angiography is less commonly performed used nowadays, but may
still have a role when planning surgery

Renal artery stenosis (RAS)

49

 The current evidence favours medical therapy in these patients, that is, an antiplatelet
agent (aspirin), lipid lowering therapy (simvastatin) and tight blood pressure control
(amlodipine).
RAS is often unmasked when patients commence an ACE inhibitor, as these drugs reduce
vasoconstriction in the efferent arterioles, which in turn reduces glomerular filtration
pressure. In patients with critical RAS this can often prompt a precipitous drop in
glomerular filtration rate.
The recently reported ASTRAL trial was a randomised controlled trial (RCT) comparing
medical and interventional (renal artery angioplasty and stenting) approaches to treating
RAS.
It found that revascularisation carried significant risks and conferred no significant clinical
benefit.
There is some controversy over the trial recruitment strategy as it only included patients
with established RAS where the responsible clinician was "unsure if revascularisation
would be beneficial", but for now current practice is to avoid routine referral for intervention
in newly diagnosed RAS.
It is most important to control his blood pressure, but with an alternative to ACE inhibition
in the first instance. Cautious, low dose ACE inhibition is sometimes an option in these
patients when other agents have failed to reduce the blood pressure, but this should only
occur under close supervision.

Renal artery stenosis is a potential cause of hypertension.

Typically patients are vasculopaths and poor prognosis (80% mortality at five years) is
related to concurrent coronary disease.
It is almost exclusively caused by atherosclerosis, but other causes include fibromuscular
dysplasia, vasculitis and external compression.
Typical ultrasound changes are asymmetrical kidneys; the affected kidney >2 cm smaller
than the unaffected kidney.

50

 ACE inhibitors are contraindicated in renal artery stenosis as they inhibit the contraction of
the efferent arterioles which promote glomerular filtration in the disease.

Retroperitoneal fibrosis
Lower back pain is the most common presenting feature
Associations
1) Riedel's thyroiditis
2) previous radiotherapy
3) sarcoidosis
4) inflammatory abdominal aortic aneurysm
5) drugs: methysergide

Renal stones
Risk factors
1) dehydration
51

2) hyperparathyroidism, hypercalciuria, hypercalcaemia

3) cystinuria
4) high dietary oxalate
5) renal tubular acidosis
6) medullary sponge kidney, polycystic kidney disease
7) beryllium or cadmium exposure
Risk factors for urate stones
1) gout
2) ileostomy: loss of bicarbonate and fluid results in acidic urine, causing the precipitation
of uric acid
Drug causes
1) drugs that promote calcium stones: steroids, loop diuretics, acetazolamide, theophylline
2) thiazides can prevent calcium stones (increase distal tubular calcium resorption)

Imaging
The table below summarises the appearance of different types of renal stone on x-ray

Type

Frequency

Radiograph appearance

Calcium oxalate

40%

Opaque

Mixed calcium oxalate/phosphate

stones

25%

Opaque

Calcium phosphate

10%

Opaque

Triple phosphate stones*

10%

Opaque

Urate stones

5-10%

Radio-lucent

Cystine stones

1%

Semi-opaque, 'ground-glass' appearance

Xanthine stones

<1%

Radio-lucent

stag-horn calculi
Involve the renal pelvis and extend into at least 2 calyces.
They develop in alkaline urine and are composed of struvite (ammonium magnesium
phosphate, triple phosphate).
52

 Ureaplasma urealyticum and Proteus infections predispose to their formation (Urease

producing bacteria )

Renal stones management:

Acute management of renal colic
Medication
the British Association of Urological Surgeons (BAUS) recommend diclofenac
(intramuscular/oral) as the analgesia of choice for renal colic*
BAUS also endorse the widespread use of alpha-adrenergic blockers to aid ureteric stone
passage
*Diclofenac use is now less common following the MHRA warnings about cardiovascular risk.
It is therefore likely the guidelines will change soon to an alternative NSAID such as naproxen
Imaging
patients presenting to the Emergency Department usually have a KUB x-ray (shows 60% of
stones)
The imaging of choice is a non-contrast CT (NCCT). 99% of stones are identifiable on
NCCT. Many GPs now have direct access to NCCT
Stones < 5 mm will usually pass spontaneously.
Lithotripsy and nephrolithotomy may be for severe cases.
Prevention of renal stones
A) Calcium stones may be due to hypercalciuria, which is found in up to 5-10% of the general
population.
1) high fluid intake
2) low animal protein,
3) low salt diet (a low calcium diet has not been shown to be superior to a normocalcaemic
diet)
4) thiazides diuretics (increase distal tubular calcium resorption)
B) Oxalate stones:
TTT:
cholestyramine reduces urinary oxalate secretion
pyridoxine reduces urinary oxalate secretion
Oxalate stones are uncommon in dietary excess of oxalate.
53

 However enteric oxaluria may occur in a number of disorders in which malabsorption results
in excessive colonic absorption of oxalate. These include:
1) Coeliac disease
2) Crohn's disease
3) Chronic pancreatitis, and
4) Short bowel syndrome.
High fluid intake and calcium carbonate are mainstay of prevention.
C) Uric acid stones
allopurinol
urinary alkalinization e.g. oral bicarbonate

Renal stones
Type of

Percentage of

stones

Features

Calcium

Hypercalciuria is a major risk factor (various causes)

Hyperoxaluria may also increase risk
Hypocitraturia increases risk because citrate forms

complexes with calcium making it more soluble

Hyperuricosuria may cause uric acid stones to which calcium

oxalate

all calculi

85%

oxalate binds
Stones are radio-opaque (less than calcium phosphate stones)

Cystine

Inherited recessive disorder of transmembrane cystine

1%

transport leading to decreased absorption of cystine from

Uric acid

intestine and renal tubule

Multiple stones may form
Relatively radiodense because they contain sulphur

Uric acid is a product of purine metabolism

May precipitate when urinary pH low
May be caused by diseases with extensive tissue

breakdown e.g. malignancy

More common in children with inborn errors of metabolism
54

5-10%

Type of
stones

Percentage of
Features

Calcium

Radiolucent

May occur in RTA, high urinary pH increases supersaturation

of urine with calcium and phosphate

RTA types 1 and 3 increase risk of stone formation (types 2

and 4 do not)
Radio-opaque stones (composition similar to bone)

Stones formed from magnesium, ammonium and phosphate

Occur as a result of urease producing bacteria (and are thus

associated with chronic infections)

Under the alkaline conditions produced, the crystals can

precipitate
Slightly radio-opaque

phosphate

Struvite

all calculi

10%

2-20%

Effect of urinary pH on stone formation

Urine pH will show individual variation (from pH 5-7).

Post prandially the pH falls as purine metabolism will produce uric acid.
Then the urine becomes more alkaline (alkaline tide).
When the stone is not available for analysis the pH of urine may help to determine which stone
was present.

Stone type

Urine acidity

Mean urine pH

Calcium phosphate

Normal- alkaline

>5.5

Calcium oxalate

Variable

55

Stone type

Urine acidity

Mean urine pH

Uric acid

Acid

5.5

Struvate

Alkaline

>7.2

Cystine

Normal

6.5

Causes of Sterile pyuria:

1) partially treated UTI
2) urethritis e.g. Chlamydia
3) renal tuberculosis
4) renal stones
5) appendicitis
6) bladder/renal cell cancer
7) adult polycystic kidney disease
8) analgesic nephropathy

Renal cell cancer

Renal cell cancer is also known as hypernephroma
Accounts for 85% of primary renal neoplasms.
It arises from proximal renal tubular epithelium
Associations*
1) more common in middle-aged men
2) smoking
56

3) von Hippel-Lindau syndrome

4) tuberous sclerosis
*incidence of renal cell cancer is only slightly increased in patients with ADPCKD
Features:
1) classical triad: haematuria, loin pain, abdominal mass
2) pyrexia of unknown origin FUO
3) left varicocele (due to occlusion of left testicular vein)
4) endocrine effects:

may secrete erythropoietin (polycythaemia),

renin,
PTH (hypercalcaemia),
ACTH

5) 25% have metastases at presentation

Management:
1) for confined disease a partial or total nephrectomy depending on the tumour size
2) alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat
patients with metatases
3) receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib) have been shown to have
superior efficacy compared to interferon-alpha

Coronal CT scan of a middle-aged woman with renal cell cancer. Note the heterogeneously enhancing mass
at the upper pole of the right kidney

57

Left: normal kidney. Right: 'clear-cell' pattern of renal cell carcinoma

'Clear-cell' pattern of renal cell carcinoma - clear cytoplasm, small nuclei

This CT demonstrates a huge left sided renal mass that is extending into the renal vein/IVC and is most likely
a renal cell carcinoma.
58

Wilms' tumour
Wilms' nephroblastoma is one of the most common childhood malignancies.
It typically presents in children under 5 years of age, with a median age of 3 years old
Features:
abdominal mass (most common presenting feature)
painless haematuria
flank pain
other features: anorexia, fever
unilateral in 95% of cases
metastases are found in 20% of patients (most commonly lung)
Associations:
1) hemihypertrophy
2) Beckwith-Wiedemann syndrome: an inherited condition associated with organomegaly,
macroglossia, abdominal wall defects, Wilm's tumour and neonatal hypoglycaemia.
3) as part of WAGR syndrome with Aniridia, Genitourinary malformations, mental
Retardation,also WT1 gene deletion.
4) one-third of cases are associated with a mutation in the WT1 gene on chromosome 11
Aniridia (absence of the iris)
The G is sometimes instead given as "gonadoblastoma," since the genitourinary
anomalies are tumours of the gonads (testes or ovaries).
(A subset of WAGR syndrome patients shows severe childhood obesity; the
acronym WAGRO (O for OBESITY) used to describe this category)
Management:
nephrectomy
chemotherapy
radiotherapy if advanced disease
prognosis: good, 80% cure rate

59

Histological features include epithelial tubules, areas of necrosis, immature glomerular structures, stroma with
spindle cells and small cell blastomatous tissues resembling the metanephric blastema

Renal transplant
HLA typing and graft failure
The human leucocyte antigen (HLA) system is the name given to the major histocompatibility
complex (MHC) in humans.
It is coded for on chromosome 6.
Some basic points on the HLA system:
Class 1 antigens include A, B and C.
Class 2 antigens include DP,DQ and DR
when HLA matching for a renal transplant the relative importance of the HLA antigens are
as follows DR > B > A
Graft survival

1 year = 90%, 10 years = 60% for cadaveric transplants

1 year = 95%, 10 years = 70% for living-donor transplants

Post-op problems

ATN of graft

vascular thrombosis

urine leakage

UTI
60

Hyperacute acute rejection (minutes to hours)

due to pre-existent antibodies against donor HLA type 1 antigens (type II hypersensitivity
reaction)

rarely seen due to HLA matching

Acute graft failure (< 6 months)

Usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)

may be reversible with steroids and immunosuppressants

other causes include CMV

Causes of chronic graft failure (> 6 months)

both antibody and cell mediated mechanisms cause fibrosis to the graft (CAN)

recurrence of original renal disease (MCGN > IgA > FSGS)

Fluid therapy:
The prescription of intravenous fluids is one of the most common tasks that junior doctors
need to do.
The typical daily requirement is:
1.5 ml/kg/hr fluid - for a 80kg man around 2-3 liters/day
40-70 mmol potassium
70-150 mmol sodium
This is why the typical regime prescribed for patients is:
1 litre 5% dextrose with 20mmol potassium over 8 hours
1 litre 0.9% normal saline with 20mmol potassium over 8 hours
1 litre 5% dextrose with 20mmol potassium over 8 hours
The amount of fluid patients require obviously varies according to their recent and past
medical history. For example a patient who is post-op and is having significant losses from
drains will require more fluid whereas a patient with heart failure should be given less fluid to
61

avoid precipitating pulmonary oedema.

The table below shows the electrolyte concentrations (in millimoles/litre) of plasma and the
most commonly used fluids:
Na+

Cl-

K+

HCO3- Ca2+

Plasma

135145

98105

3.55

22-28

2.32.6

0.9% normal
saline

150

150

5% dextrose

Hartmann's
solution

131

111

29

Hyponatraemia:
Hyponatraemia may be caused by water excess or sodium depletion.
Causes of pseudohyponatraemia include
Hyperlipidaemia (increase in serum volume) or a
taking blood from a drip arm.
Urinary sodium and osmolarity levels aid making a diagnosis
Urinary sodium > 20 mmol/l
Sodium depletion, renal loss (patient often hypovolaemic)
diuretics
Addison's
diuretic stage of renal failure
62

Patient often euvolaemic:

SIADH (urine osmolality > 500 mmol/kg)
Hypothyroidism
Urinary sodium < 20 mmol/l
Sodium depletion, extra-renal loss
diarrhoea, vomiting, sweating
burns, adenoma of rectum
Water excess:
(Patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, cirrhosis
reduced GFR: renal failure
IV dextrose,
psychogenic polydipsia

Hyponatraemia: correction
Central pontine myelinolysis
demyelination syndrome caused by rapid correction of chronic hyponatraemia
may lead to quadriparesis and bulbar palsy
diagnosis: MRI brain

Hypernatraemia:
Causes
dehydration
osmotic diuresis e.g. HONK coma
DI
63

 excess IV saline
Cerebral oedema:
Hypernatraemia should be corrected with great caution. Although brain tissue can lose sodium
and potassium rapidly, lowering of other osmolytes (and importantly water) occurs at a slower
rate, predisposing to cerebral oedema
Resulting in seizures, coma and death.
It is generally accepted that a rate of no greater than 0.5 mmol/hour correction is appropriate.

hypokalaemia:
ECG features of hypokalaemia
U waves
small or absent T waves (occasionally inversion)
prolong PR interval
ST depression
long QT
The ECG below shows typical U waves. Note also the borderline PR interval

One registered user suggests the following rhyme

In Hypokalaemia, U have no Pot and no T, but a long PR and a long QT
ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS
leading to a sinusoidal pattern and asystole.

64

Hypomagnesaemia:

Causes:
Diuretics, gittelman syndrome
total parenteral nutrition TPN
diarrhoea
alcohol
hypokalaemia, hypocalcaemia
Features:
hypocalcaemia
paraesthesia
tetany
seizures
arrhythmias
decreased PTH secretion hypocalcaemia
exacerbates digoxin toxicity
ECG features similar to those of hypokalaemia

Hypermagnesaemia:

Nausea, Drowsiness
Double vision
Vasodilatation, and
Hypotension (myocardial depression + vasodilatation).
Bradycardia
Respiratory depression
Loss of deep tendon reflexes
Coma, and
Cardiac arrest.

Hypophosphataemia:
Causes:
alcohol excess
acute liver failure
DKA
refeeding syndrome
primary hyperparathyroidism
osteomalacia
Consequences:
65

haemolysis
WBC and platelet dysfunction
muscle weakness and rhabdomyolysis
CNS dysfunction

The following notes are some comments on important questions from on examination I did not
have time to rearrange it now may be latter on I will rearrange.
Oxalate stone
Hyperoxaluria occurs both in patients with an ileal resection and in patients with a
short bowel who have had a distal small bowel resection (for example, Crohn's
disease, infarcted bowel). It is caused by increased absorption of oxalate by the
colon. Bile salts in the colon increase oxalate absorption. Hyperoxaluria is associated
with renal stone formation and the propensity to form stones is reduced when
oxalate intake is reduced.
Treatment involves having a low-oxalate diet and taking cholestyramine to bind bile
salts and citrate to prevent stone formation. Low-oxalate diets typically exclude
cocoa, peanut products, tea, coffee, wheat germ, rhubarb, beetroot, spinach, tofu
and soybeans and restrict certain citrus drinks (lemon juice is a natural source of
citrate and its consumption by oxalate stone formers can reduce stone
formation/growth), diet soda drinks, tomatoes and fruit.
In addition, calcium excretion can be reduced by using bendofluazide 5 mg daily and
regular pyridoxine 10 mg daily can reduce hyperoxaluria.

Calcium phosphate stones can be prevented with thiazide diuretics and a low
calcium diet (restrict dairy products).
Triple phosphate stones often cause staghorn calculi and patients require
prophylactic antibiotics to prevent recurrent infections; these stones may require
surgery for removal.
66

Urate stones may be prevented by giving regular allopurinol and by urinary

alkalinisation.
Methods of preventing cysteine stones include adequate hydration (increase
daily fluid intake), low methionine diet, D-penicillamine and urinary
alkalinisation.

Acute interstitial nephritis

characterised by interstitial inflammation and oedema.
Left untreated this results in interstitial fibrosis. A definitive diagnosis is established
by renal biopsy, although eosinophiluria and gallium 67 scanning are also suggestive.
60-70% of cases of acute interstitial nephritis are induced by exposure to drugs. The
mechanism is via a delayed T-cell hypersensitivity or cytotoxic T-cell reaction.
This is not typically dose-dependent. Multiple medications have been implicated, and
the presentation and laboratory findings vary according to the class of drug involved.
Agents which are commonly implicated are:
beta-lactam antibiotics (especially methicillin)
sulphonamides
NSAIDs
diuretics (thiazides, furosemide)
antivirals (aciclovir, foscarnet)
allopurinol, and
cyclosporin.
Classic presenting features include fever, maculopapular rash and arthralgia. Mild
eosinophilia is common, and eosinophiuria is pathognomonic.
Cessation of the causative agent is critical in the treatment of acute interstitial
nephritis.
Corticosteroids can have a beneficial effect, especially if initiated early.
In general, the prognosis of drug-induced acute interstitial nephritis is good, and
partial or complete recovery of renal function is normally seen.

Goodpasture's disease is an auto-immune pulmonary renal syndrome due to

circulating antibody to the glomerular basement membrane.
In the acute setting, treatment is focused on managing life threatening complications
of renal failure, such as hyperkalaemia, and removing the circulating auto-antibody
responsible for disease.
67

As this patient is receiving haemodialysis, the most important treatment in acute

setting is plasmapharesis (therapeutic plasma exchange), as this will remove the
circulating antibody.
There is no role for intravenous immunoglobulins in the management of this disease.

In this scenario, the recent prescription of NSAIDs after the patient's hospital
attendance is the likely cause of the renal decline. NSAIDs reduce glomerular
perfusion by inhibiting production of prostaglandins which dilate the afferent arteriole
of the glomerulus. The reduction in blood supply to the kidney results in impairment
of kidney function.
As a rule, one should be cautious about prolonged prescription of NSAIDs in the
elderly, or in those with existing renal impairment.

HIV nephropathy is characterised by:

raised creatinine
nephrotic range proteinuria
normal sized kidneys on ultrasound scan, and
focal segmental glomerulosclerosis on renal biopsy.
Patients also have raised immunoglobulins and raised cholesterol.
Somewhat surprisingly the blood pressure of patients with HIV nephropathy is usually
normal.
Prior to the availability of HAART (highly active anti-retroviral therapy), mean time to
progression to end-stage renal failure was 2.5 months, however in the post-HAART
era, the renal prognosis has significantly improved.
The pathogenesis of HIV associated nephropathy is unclear, and may be multi-modal
involving direct effects of the HIV virus itself, the impact of cytokines, and differential
expression of immune cells in patients who develop the disorder.

Recommendations from a clinical review target a reduction in blood pressure of

around 25% during the first 24-48 hours of therapy for accelerated hypertension
68

where the patient falls into the hypertensive "emergency" as here, rather than the
hypertensive "urgency" category.
The concern is that if blood pressure reduction is targeted more aggressively,
disordered autoregulation may result in significant end organ damage.
IV therapy with either sodium nitroprusside or labetolol is the initial therapy of
choice.
Alternatives include phentolamine or hydralazine.

Renal vein thrombosis is often clinically silent. Association with hypercoagulable

state, peripheral leg oedema and flank pain in a patient presenting with AKI are all
pertinent clues.
Patients with renal vein thrombosis usually report rapidly worsening peripheral leg
oedema, and may report dull loin pain from the affected kidney.
This patient requires screening for inherited and acquired disorders of coagulation
and anti-coagulation. She will require lifelong warfarinisation.

Acute interstitial nephritis is inflammation of the renal tubulo-interstitium, secondary

to a hypersensitivity reaction to drugs. The most common drug related cause is
NSAIDs.
Other precipitating drugs include
Antibacterials (penicillins, cephalosporins, sulphonamides, rifampicin)
Loop diuretics (furosemide)
Thiazide diuretics
Amphotericin
Cimetidine
Allopurinol.
69

Features include acute, most commonly oliguric renal failure, with or without
systemic features which include fever, arthralgia and skin rashes. Many patients
have eosinophilia, raised serum IgE and eosinophiluria.
Renal biopsy shows oedema of the interstitum with infiltration of plasma cells,
lymphocytes and eosinophils, with acute tubular necrosis and variable tubular
dilatation.
The treatment includes withdrawal of the offending drug, and may involve dialysis
until normal renal function returns.

Angiotensin-converting enzyme (ACE) inhibitors can cause acute deterioration in

renal function, mainly in patients with bilateral renovascular disease, and commonly
within the first two weeks of treatment. ACE inhibitors may also increase the serum
potassium, through impairment of the angiotensin II mediated secretion of
aldosterone. The higher the serum creatinine concentration, the greater the risk of
hyperkalaemia.
Uncommonly, ACE inhibitors may cause progressive renal impairment in patients
without renovascular disease, especially the elderly, which may be caused by a
membranous glomerulonephritis.
Bendroflumethiazide, a thiazide diuretic, inhibits sodium and chloride reabsorption in
the distal convoluted tubule, resulting in increased sodium and free water clearance.
A secondary effect is the loss of potassium by increased secretion in the distal tubule
in response to the increased intraluminal sodium. Therefore, bendroflumethiazide
may cause hypokalaemia.
Triamterene, a potassium sparing diuretic similar to amiloride, is occasionally
prescribed with thiazide or loop diuretics, to prevent hypokalaemia. It inhibits the
movement of sodium through channels towards the end of the distal tubule and
collecting ducts, preventing the passage of sodium from the urinary space into the
tubular cells. This action causes hyperpolarisation of the apical plasma membrane,
preventing the secretion of potassium into the collecting ducts. Hyperkalaemia is
common (>5%), and is unaffected by concurrent potassium depleting diuretics.
Bartter's syndrome is a rare, autosomal recessive disorder, caused by one of three
mutations of the ion transporter or ion channel present in the thick ascending limb of
the distal nephron.
Type I and II mutations present in infancy (often following premature birth and
polyhydramnios) with severe dehydration, hypokalaemic alkalosis, hypercalciuria and
nephrocalcinosis. Mortality is high.
Type III mutations present with a more varied clinical picture to type I and II, ranging
in severity from near fatal volume depletion with hypokalaemic alkalosis and
respiratory arrest, to mild disease presenting in teenagers with weakness and
polyuria.
70

Nephrocalcinosis has not been described in type III mutations, therefore it can
differentiate between type I and II disease, and type III disease.
Management is with long term potassium supplementation and care to avoid
dehydration. The long term prognosis is uncertain.

This patient has had a sudden deterioration in renal function, three weeks following
an uncomplicated renal transplant. Despite this, she is clinically well, with no
symptoms.
This lady has acute cellular rejection. Approximately 25% of transplant patients will
have at least one episode of rejection mostly between days seven and 21, and less
commonly up to three months post-operation. It is often clinically silent, with only a
sharp rise in serum creatinine pointing towards the diagnosis.
Doppler ultrasound studies may show a sharp deterioration in graft perfusion, and
kidney biopsy will show invading lymphocytes penetrating the tubular basement
membrane, causing tubulitis. Treatment is with IV bolus of high dose steroids. Long
term graft function will be compromised if the rejection episode is not completely
reversed.
CMV infection has been associated with increased graft rejection and renal artery
stenosis in renal transplant recipients.
Ciclosporin is a calcineurin inhibitor which is a potent immunosuppressant and
nephrotoxin. Ciclosporin can cause a dose dependent increase in urea and creatinine
in the first few weeks of taking, and also long term graft failure. This is probably
related to the total amount of ciclosporin taken. in the question they will mention
that the dose has recently been increased
Pyelonephritis of the transplanted kidney is a particular problem in the early
immunosuppressed period. Pyelonephritis would present with low grade pyrexia,
tender, swollen kidney and deteriorating graft function.
This lady has longstanding rheumatoid arthritis treated with gold. She currently has
an exacerbation of her symptoms. She has renal impairment with mild proteinuria
and haematuria.
Amyloid is common in patients with longstanding rheumatoid arthritis. The fibrils are
amyloid A protein. It presents with proteinuria that is often nephrotic range.
Gold nephropathy causes proteinuria, which is often in the nephrotic range.
Haematuria is rare, as is an abnormal renal function.
Non-steroidal anti-inflammatory drugs (NSAIDs) may cause:
A reversible reduction in the glomerular filtration rate
Acute tubular necrosis
Acute interstitial nephritis often with heavy proteinuria
Renal papillary necrosis, and
Chronic tubulointerstitial nephritis.
71

The clinical presentation in rheumatoid includes

Nail fold infarcts
A leucocytoclastic vasculitis
A peripheral neuropathy
Pericarditis
Gastrointestinal infarcts and
Renal vasculitis.
Renal abnormalities are found in 25% of patients with rheumatoid vasculitis, usually
presenting with proteinuria, microscopic haematuria and renal impairment.

Bartter's syndrome usually presents in childhood with severe muscle weakness. It is

a salt wasting state, which is due to a defect in the loop of Henle chloride
reabsorption (at the Na+-K+ -2Cl- cotransporter). Patients have low blood pressure
and severe hyperreninaemia.
Conn's syndrome is caused by an adrenal adenoma secreting aldosterone. The
clinical features include hypertension, hyperaldosteronism, hypokalaemia and
hyporeninaemia.
Essential hypertension is not associated with endocrine or electrolyte abnormalities.
In patients younger than 35 with hypertension, an endocrine cause should be
excluded.
Fibromuscular dysplasia, a rare cause of hypertension and hypokalaemia is more
common in women. It causes hyperreninaemic hyperaldosteronism.
Liquorice ingestion causes a primary aldosterone type picture. It is caused by
glycyrrhizic acid contained in liquorice, blocking the enzyme 11b hydroxysteroid
dehydrogenase. This prevents the inactivation of cortisol, which in turn activates
mineralocorticoid receptors in the kidney.
This gentleman has a nephrotic syndrome with impairment of his renal function,
which improves markedly with oral prednisolone.
Mesangiocapillary glomerulonephritis is treated with antiplatelet drugs,
anticoagulants, corticosteroids and alkylating agents. Steroids are given for a
prolonged period of time, and may have some benefit in some patients.
72

Minimal change glomerulonephritis is extremely steroid sensitive, with 80% of adult

patients achieving remission within 16 weeks with prednisolone 60 mg per day.

This gentleman has had a calcium urinary tract stone. He has normal serum calcium,
but raised urinary excretion of calcium.
Idiopathic hypercalciuria is often familial, the most common cause being increased
gastrointestinal absorption of calcium. The most common stones are calcium oxalate
stones.
In this patient, his urinary output is 1150 ml/24 hr. He should aim for a daily urinary
output in excess of 2000 ml. The correct answer is therefore to advise him to
increase his fluid intake.
A high protein intake is associated with urinary stones, and by reducing his dairy
dietary intake he may reduce his gastrointestinal absorption of calcium, but the main
initial treatment is to increase his urine volume.
Potassium citrate and potassium bicarbonate can be used to alkalinise the urine, to
prevent the formation of cystine containing stones. Potassium citrate also chelates
calcium and is useful in combination with thiazides in those who develop
hypokalaemia on diuretics.
Thiazide diuretics reduce renal tubular calcium excretion, and therefore can prevent
calcium stone formation.
Loop diuretics increase urinary excretion of calcium, and therefore would exacerbate
calcium renal stone formation.

Usually the MPO antibody is associated with microscopic polyangiitis, whereas the
PR3 antibody is associated with Wegener's granulomatosis, which is closely linked.

Renal biopsy:
For a routine biopsy there is no preferable side to biopsy.
Coagulation studies should always be performed prior to renal biopsy due to the risk
of bleeding. Macroscopic haematuria can occur in up to 10% of renal biopsies.
The hila of the kidneys lie at the L1 and L2 vertebral levels.
Nephrectomy is a rare but serious complication of renal biopsy required to control
bleeding. It should be consented for.

73

Dairy products are high in phosphate content. Of the foods listed, cheddar cheese
will contain the highest phosphate.
Phosphate level is important to control in patients with chronic renal failure.
Although high phosphate can cause symptoms such as itching, there are long term
adverse cardiovascular effects.
Foods that are characteristically rich in phosphate include dairy products, fibre rich
foods, chocolate, and processed meats.

Kidney transplant recipients have a high risk of developing non-melanoma skin

cancer.
Cancer surveillance is an important consideration in kidney transplant recipients.

Extended spectrum beta lactamase (ESBL)

This patient has an ESBL urine infection and is symptomatic. Meropenem has a broad
spectrum of activity and is the right initial course of antibiotics in this case pending
full sensitivities of the cultured organism.
ESBL infections are becoming a greater problem in hospitals. These organisms have
broader beta lactamases; enzymes capable of breaking down a larger variety of
antibiotics.
In this patient, the presence of renal cysts, a reservoir of infection and previous
antibiotic use are likely to have led to this resistant strain.
A broad spectrum antibiotic is required and of the list available, meropenem is the
most suitable choice.
Intravenous co-amoxiclav is unlikely to be adequate. Neither would erythromycin
have the appropriate coverage.

74

In acute gout with renal impairment, a trial of colchicine is the best option
Colchicine is safe to use in renal impairment. It is generally advised to be taken to
the point of onset of diarrheal symptoms, when its use should be discontinued. So
long as the patient is adherent with the advise, renal function should not deteriorate
The first line treatment for acute gout is a non-steroidal anti-inflammatory drug
(NSAID) or colchicine. Given this patient's renal impairment, a NSAID would be
contraindicated.
Paracetamol will offer some mild pain relief but will not treat gout and so is not
appropriate.
Allopurinol should not be started in an acute attack of gout.
Prednisolone is a reasonable choice but is usually tried as a second line treatment
after NSAID use or colchicine.

In the setting of diabetes and stable renal function the albumin:creatinine ratio is
considered the most appropriate test to detect and quantify proteinuria. Ideally the
test should be performed on an early morning sample.
It is more sensitive than the protein:creatinine ratio for low levels of proteinuria and
more reliable than a 24 hour urinary collection for protein.
The albumin:creatinine ratio is the test of choice in patients with diabetes due to the
need to detect and treat microalbuminuria.
Twenty four hour urine collections for protein are fraught with difficulty. Despite often
being referred to as the 'gold standard' for measuring proteinuria they are subject to
inaccuracies due to incomplete collection of all urine voided or inaccurate timing,
and the biochemical methods used to quantify the amount of protein present give
different results.
For low levels of proteinuria the PCR is less sensitive than ACR. Once significant
proteinuria has been detected the PCR may be used for follow up.
75

Urine dipsticks are not recommended as a method for accurately determining

whether there is proteinuria as they cannot reliably detect low-level protein loss or
quantify the amount.
Urine protein electrophoresis may be used if there is a suspicion of a urinary
paraprotein (that is, Bence Jones proteins).

Microalbuminuria is defined as an ACR of 2.5-30 mg/mmol in men and 3.5-30

mg/mmol in women. This is roughly equivalent to the loss of 30-300 mg of albumin in
the urine per 24 hours.
In patients with diabetes, microalbuminuria is used as a therapeutic target that can
be modified by renin-angiotensin-aldosterone system blockade with a resulting
improvement in clinical outcomes.
All patients with diabetes and microalbuminuria should be offered therapy with an
ACE inhibitor or angiotensin receptor blocker irrespective of whether they have
hypertension. The chosen drug should be started at an appropriate starting (low)
dose and titrated upwards to the target dose as tolerated with monitoring of renal
function.
The predominant protein lost in urine is albumin and the albumin:creatinine ratio is a
significantly more sensitive test for low level proteinuria than the protein:creatinine
ratio.
In patients with diabetes the albumin:creatinine ratio should always be used in order
to determine whether or not there is clinically significant renal protein loss. Once
established the protein:creatinine ratio may be used for follow-up measurements
though the ACR is usually recommended in patients with diabetes.
Where the initial result is borderline the albumin:creatinine ratio should be repeated
on an early morning urine sample (a morning sample is best as the urine is most
concentrated and thus the concentration of protein will be highest and more likely to
be detected). This is recommended in non-diabetic patients with an initial ACR of 3070 mg/mmol.

76

In polycystic kidney disease

Magnetic resonance angiography is usually only recommended in patients with a
diagnosis of polycystic kidney disease who have symptoms of an intracranial
aneurysm (ICA), a previous ICA, a high-risk job should intracranial haemorrhage
occur or an affected family member with an ICA.

The National Institute for Health and Care Excellence guidelines on the identification
and management of chronic kidney disease recommend that screening for chronic
kidney disease should be offered to patients with:
Diabetes
Hypertension
Cardiovascular disease
Structural renal tract pathology
Multisystem disease with potential renal involvement
Opportunistically detected haematuria or proteinuria
A family history of stage 5 chronic kidney disease, or
Hereditary kidney disease.
In the absence of other risk factors the guidelines recommend that age, gender and
ethnicity should not be used as risk markers to test people for chronic kidney
disease.
Obesity alone should not be used as a risk factor (features of the metabolic
syndrome should also be present).

The NICE guidelines on the management of Chronic kidney disease

(CG182) recommend that patients with chronic kidney disease who have proteinuria
equivalent to ACR 70 mg/mmol should have their blood pressure controlled to the

77

target range 120-129/<80 mmHg. The same target range should be used in patients
with diabetes.
The NICE guidelines recommend that a blood pressure target range of 120-139/<90
mmHg should be used in non-diabetic patients with chronic kidney disease and an
ACR <70 mg/mmol.
Aiming for lower systolic (<120 mmHg) or diastolic (<60 mmHg) blood pressures
increases the risk of mortality, cardiovascular disease, congestive cardiac failure and,
in the case of low diastolic values, progression of chronic kidney disease.
Systolic or diastolic blood pressures above the target ranges are associated with
increased risk of a doubling in serum creatinine, end-stage renal failure and death.

Hypertension, diabetes and the presence of proteinuria are well-recognised and

accepted risk factors for the progression of chronic kidney disease (CKD).
Cardiovascular disease is also a known risk factor for progression in chronic renal
impairment.
In patients with chronic kidney disease these risk factors should be actively managed
to slow any fall in glomerular filtration rate.
Aspirin usage has been suggested as a possible risk factor for the progression of
chronic kidney disease. However it is widely used in patients with cardiovascular
disease, which in itself is a risk factor for progression of chronic kidney disease. This
is a significant confounding factor in the evidence base investigating a link between
the drug and progressive decline in glomerular filtration rate.
The evidence that smoking and ethnicity (Afro-Caribbean and Asian ethnicity) are risk
factors for CKD progression is suggestive but inconclusive.
There is no significant evidence that obesity affects the progression in CKD.
Short term non-steroidal anti-inflammatory drug use is associated with a reversible
decline in glomerular filtration rate. Chronic use in patients with CKD may be
associated with a progressive and irreversible fall in glomerular filtration rate.

78

Transferrin saturation <20% is a marker of functional iron deficiency (when the

ferritin is >100 g/L). It is recommended that patients with anaemia secondary to
chronic renal failure should have a ferritin level maintained at 200-500 g/L and
either transferrin saturations >20% or percentage hypochromic red cells <6%.

This patient has severe and potentially life-threatening hyperkalaemia with changes
on the ECG.
The first step in treatment must be to administer calcium gluconate in order to
stabilise the myocardium. However remember that definitive treatment to reduce the
potassium level needs to be initiated soon after.
Calcium resonium is an ion exchange resin which, when taken orally, prevents
potassium from being absorbed in the diet. It acts to deplete the body of potassium
(by preventing absorption) and takes at least 24-48 hours to have an effect. It is not
suitable as an emergency treatment.
The definitive treatment for this patient's hyperkalaemia and acidosis will be
haemodialysis however this may take a little time to instigate and in the meantime
treatment must be instituted in order to stabilise the myocardium. Holding measures
such as insulin/dextrose infusions may not be necessary if dialysis can be organised
rapidly.
Nebulised salbutamol may be effective in lowering the serum potassium
concentration however it should be noted that up to 40% of patients who are
dependent upon dialysis do not demonstrate a fall in serum potassium in response to
nebulised salbutamol.
This patient has a metabolic acidosis which will be related to his renal failure and
contributing to the hyperkalaemia (potassium moves out of cells as hydrogen ions
are moved into cells in order to buffer the extracellular pH).
Despite this sodium bicarbonate is not generally recommended for the treatment of
acute hyperkalaemia as it may fail to lower the serum potassium, can take up to 60
minutes to work and is associated with potential sodium and volume overload.
79

This patient has chronic kidney disease and due to a consequent deficiency of
activated vitamin D has developed tertiary hyperparathyroidism.
Biochemically this is characterised by raised calcium, raised (or sometimes normal)
phosphate and grossly elevated parathyroid hormone levels. The most appropriate
treatment once this has developed is parathyroidectomy.
Cinacalcet is a calcimimetic agent which mimics the effect of calcium on the
parathyroid gland. It is effective in controlling excess parathyroid hormone
production and reducing calcium levels in tertiary hyperparathyroidism however it is
currently recommended only in patients who are not fit for surgical
parathyroidectomy.
Lanthanum and sevelamer are both non-calcium containing phosphate binders which
may be used, in conjunction with diet, to control high phosphate levels seen in
chronic renal failure.
Bisphosphonates such as pamidronate do not have a role in the management of
hypercalcaemia in renal bone disease.

This patient has evidence of secondary hyperparathyroidism and

hyperphosphataemia as a result of chronic renal failure.
A calcium containing phosphate binder such as calcium acetate would be an
appropriate first treatment to try. In conjunction with dietary phosphate restriction
this will help reduce the plasma phosphate and the additional calcium may well be
sufficient to increase the plasma calcium enough to bring it into the normal range.
Adcal-D3 is not recommended for use in chronic renal disease as the vitamin D it
contains is non-activated and the presence of renal failure means that it cannot be
activated in the kidney. The calcium carbonate it contains could act as a phosphate
binder if taken in the appropriate manner (with meals).
80

Alfacalcidol is 1-hydroxylated vitamin D and is used when vitamin D

supplementation is required in chronic renal failure in order to maintain the calcium
within the normal range and control the levels of parathyroid hormone.
A slightly elevated parathyroid hormone level is actually desirable in the
management of renal bone disease. Suppression is not generally necessary until
levels exceed 300 ng/L.
sevelamer is phosphate binders - whilst they would help correct the elevated
phosphate they would not have any impact on the low calcium.

The patient has nephritic syndrome, and the most likely cause of this is postinfectious glomerulonephritis. Wire-loop lesions may be seen in this condition. A wireloop lesion is a capillary loop with immune complex deposition circumferential
around the loop. They may also be seen in lupus nephritis.
Nephritic syndrome consists of:
Oliguria
Acute renal failure
Haematuria
Hypertension
Proteinuria
Oedema
Outcome and treatment of nephritic syndrome depends on renal biopsy.
Post-infectious glomerulonephritis is a diffuse proliferative glomerulonephritis with
proliferation of capillaries, obliteration of capillary loops and 'wire-loop' lesions on
light microscopy. There is antibody and compliment deposition on immunostaining.
Crescentic glomerulonephritis occurs in IgA nephropathy, small vessel vasculitis,
Goodpasture's disease and systemic lupus erythematosus (SLE). It is less common in
post-infectious glomerulonephritis.

81